Chr t(11;14)

P3, N=529, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Jan 2026

P3, N=547, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2025 --> Jan 2026

FISH demonstrated a t(11;14)(q13;q32) translocation and a gain of 1q. Despite treatments with daratumumab, bortezomib, lenalidomide, dexamethasone, and autologous stem cell transplant, the patient ultimately expired from streptococcal pneumonia with hypoxic respiratory and subsequent multiorgan failure.

P2, N=120, Recruiting, Mayo Clinic | Trial completion date: Mar 2031 --> Oct 2031 | Trial primary completion date: Mar 2030 --> Oct 2030

P1/2, N=8, Active, not recruiting, City of Hope Medical Center | Trial completion date: Nov 2024 --> Mar 2025 | Trial primary completion date: Nov 2024 --> Mar 2025

Despite achieving remission with intensive chemotherapy, the patient experienced rapid relapse and poor overall survival, reflecting the ineffectiveness of conventional treatments. The findings highlight the synergistic role of SIL-TAL1 and t(11;14) in disease progression and underscore the urgent need for targeted therapies and immunotherapies to improve outcomes in such high-risk cases.

P2, N=120, Recruiting, Mayo Clinic | Trial completion date: Mar 2026 --> Mar 2031 | Trial primary completion date: Mar 2025 --> Mar 2030

P1/2, N=30, Recruiting, Chinese PLA General Hospital | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2026

P3, N=182, Recruiting, Hoffmann-La Roche | Trial completion date: Dec 2026 --> Jun 2027

P1, N=28, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2025 --> Jan 2026

P1, N=18, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2024 --> Jun 2025 | Trial primary completion date: Dec 2024 --> Jun 2025

P2, N=39, Recruiting, Oncotherapeutics | Trial completion date: Dec 2026 --> Dec 2027 | Not yet recruiting --> Recruiting

P2, N=15, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2024 --> Jun 2025

P1, N=7, Terminated, AstraZeneca | Phase classification: P1/2 --> P1

P2, N=622, Recruiting, Genmab | Trial completion date:Jun 2031 --> Nov 2032 | Trial primary completion date: Jun 2031 --> Nov 2032

Immunophenotypic antigens positive and negative expressions are associated with high-risk genetic abnormalities and advanced clinical stages of PCM. IEC/2017/230, AFMC, Pune.

P2, N=30, Completed, AstraZeneca | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Oct 2024

Bcl-2 protein ratios predicting sensitivity to venetoclax in vitro were also able to distinguish patients with shorter time to progression after triplet-based induction therapy and ASCT. This is the first study to assess the expression of the most important Bcl-2 family proteins by a quantitative method in a large set of MM patients according to their cytogenetic abnormalities. We shed light on the impact of these proteins on MM prognosis, which could help to consider the levels of proteins involved in apoptosis in the development of new therapeutic strategies.

P2; Trial completion date: Mar 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P2, N=141, Active, not recruiting, Fondazione Italiana Linfomi - ETS | Trial completion date: Jul 2025 --> Nov 2025

Although molecularly targeted therapies have shown efficacy in other hematologic malignancies, currently venetoclax is the only targeted therapy approved for MM (t(11;14))...It addresses gene therapies, small molecule inhibitors and monoclonal antibodies currently under investigation to antagonize oncogenic drivers including MCL-1, BCL9, F11R, and CKS1B, all of which are implicated in cell survival, proliferation or drug resistance. In conclusion, the link between chromosome 1 abnormalities and high-risk disease in MM patients offers a compelling rationale to identify and explore therapeutic targeting of chromosome 1 gene products as a novel precision medicine approach for a poorly served patient population.

P2, N=622, Recruiting, Genmab | Trial completion date: Nov 2032 --> Jun 2031 | Trial primary completion date: Nov 2032 --> Jun 2031

P2; N=45 --> 72

We then discuss currently available diagnostic approaches and we conclude with future directions. We also suggest that the more specific terms CCND2-rearranged MCL or CCND3-rearranged MCL be used for neoplasms in which the rearranged gene is known, and that we reserve the term cyclin D1-negative MCL for neoplasms in which the rearranged gene in unknown.

P2, N=30, Recruiting, Mayo Clinic | Trial completion date: Nov 2025 --> Jan 2027 | Trial primary completion date: Nov 2024 --> Jan 2027

P1, N=316, Active, not recruiting, Eli Lilly and Company | Trial completion date: Dec 2024 --> Dec 2025

P1/2, N=54, Completed, Incyte Corporation | Active, not recruiting --> Completed

P1/2, N=5, Terminated, University of Utah | N=39 --> 5 | Trial completion date: Aug 2027 --> Oct 2024 | Recruiting --> Terminated; This study was terminated due to sponsor de-activation of all programs associated with RP-3500 (camonsertib).

P2, N=622, Recruiting, Genmab | Trial completion date: Jun 2031 --> Nov 2032 | Trial primary completion date: Jun 2031 --> Nov 2032

P3, N=689, Active, not recruiting, ECOG-ACRIN Cancer Research Group | Recruiting --> Active, not recruiting | Trial completion date: Jan 2032 --> Jan 2027

Moreover, the combination of TAS0612 with venetoclax (VEN) showed the synergy in inducing apoptosis in HMCLs irrespective of the t(11;14) translocation status. TAS0612 alone and combined with VEN are new potent candidate therapeutic strategies for MM, regardless of cytogenetic/genetic profiles, facilitating its future clinical development.

P1, N=34, Active, not recruiting, AbbVie | Recruiting --> Active, not recruiting | N=360 --> 34 | Trial completion date: Aug 2026 --> Dec 2025 | Trial primary completion date: Aug 2026 --> Feb 2024

However, it should be noted that MRD diagnostics for clinical treatment protocols has to be accompanied by regular international quality control rounds to ensure the reproducibility and reliability of the MRD results. This is available by the EuroMRD network ( https://euromrd.org ), a subgroup of ESHLO ( https://eslho.org ).

P2, N=27, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed | N=50 --> 27

Overexpression of PAX5 resulted in increased CCND1 expression. These results support the importance of rs9344 G enhancer in increasing CCND1 expression in MM.

P1, N=18, Active, not recruiting, City of Hope Medical Center | Trial completion date: Jun 2024 --> Dec 2024 | Trial primary completion date: Jun 2024 --> Dec 2024

P2, N=29, Active, not recruiting, National Heart, Lung, and Blood Institute (NHLBI) | Trial completion date: Oct 2028 --> Oct 2034

P1/2, N=18, Completed, K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc. | Active, not recruiting --> Completed | N=135 --> 18 | Trial completion date: Dec 2025 --> Feb 2024 | Trial primary completion date: May 2025 --> Feb 2024

P2, N=3, Terminated, Academic and Community Cancer Research United | N=63 --> 3 | Trial completion date: Apr 2029 --> Mar 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Apr 2027 --> Mar 2024; Trial closed due to low accrual rate

P2, N=622, Recruiting, Genmab | N=394 --> 622 | Trial completion date: Nov 2032 --> Jun 2031 | Trial primary completion date: Nov 2032 --> Jun 2031

P2, N=9, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=30 --> 9

However, its distinct reliance on Bcl-2 has heightened its sensitivity to venetoclax. Further subclassification based on morphological and genomic characteristics could enhance our prediction models of treatment responses and enable more tailored therapeutic strategies for patients. This review aims to encapsulate the existing research evidence in this area.